The present invention relates to devices for administering drugs, and more particularly to devices for the prolonged internal administration of drugs to warm-blooded animals.
The medical profession has long sought devices whereby drugs could be internally administered to warm-blooded animals in a controlled fashion over prolonged intervals. As an approximation to this sought after controlled, prolonged administration, it is the common practice today to administer drugs in oral doses at fixed periods of time. This practice results in a large amount of the drug being in the patient's blood stream shortly after administration of the dose, with the concentration decreasing thereafter. If it is desired to maintain a certain minimum level of the drug in the blood stream at all times, then amounts far in excess of this minimum level must be tolerated just after the dose is administered so that the minimum amount will be present just before the next dose is administered. While this procedure is recognized to be less than desirable, it has long been followed as the method of choice.
Even so-called "sustained release," "timed release," "prolonged release" or "controlled release" dosage forms merely extend the time period over which a drug is released, without prolonging the retention of the dosage form in the environment of use. Thus, a "timed release" oral capsule provides drug release for only as long as the capsule or its contents are retained in the gastrointestinal tract without prolonging this period of retention. The retention time (dwell time) of a dosage form in, for example, the gastrointestinal tract, varies from species to species, from individual to invididual, and for the same individual under different conditions. The retention time of conventional "timed release" dosage forms in the gastrointestinal tract is about 8-12 hours.
Many prior art devices exist for the dispensing of drugs within an animal body. These devices generally fall into one of the following categories.
First, there are devices illustrated by Higuchi U.S. Pat. Nos. 3,732,865; 3,760,805; 3,929,132; and 3,995,631; and Eckenhoff U.S. Pat. No. 3,987,790. These devices generally comprise a rigid outer shell within which are two chambers, one of which chambers is impervious to body fluid and contains drug and the other of which is permeable to body fluids and contains an osmotically effective solute. Body fluid flows by osmosis into the second compartment, thereby exerting pressure upon the first compartment and forcing drug out through a hole therein.
While these "osmotic pump" devices are useful for the controlled administration of drug, they are not retained in the stomach for any longer time than a conventional capsule and hence do not provide administration of drug for a period longer than about 8 to 12 hours.
A second group of devices is exemplified by the following U.S. Patents, all assigned to Alza Corporation: Nos. 3,828,777; 3,845,770; 3,916,899; 3,977,404; 3,991,759; 4,016,880; and 4,034,758. These devices generally comprise a rigid wall surrounding a drug composition, the wall being permeable to an external fluid but substantially impermeable to the drug composition contained therein. There is a passageway in the wall through which the drug solution is expelled due to the osmotic pressure generated within the device by the flow of fluid through the wall. These devices are generally taught to be used in the eye, although other locations (including orally) are also mentioned. It is clear that these devices would not be retained in the stomach for any longer than a conventional capsule and would be expelled within about 8 to 12 hours.
Baker U.S. Pat. No. 3,952,741, relates to a device comprising a semi-permeable wall surrounding a drug composition, which wall is permeable to water but not to the drug contained therein. When the osmotic pressure inside the device is sufficiently great due to the flow of water thereinto, the wall ruptures and the drug is dispensed all at once. This device does not provide a controlled, prolonged dispensing of drug. Moreover, once the device has burst it will not be retained within the stomach any longer than the usual residence time; i.e., about 8 to 12 hours.
Recently, however, there has been work toward the development of a device which would be retained in the environment of use (e.g., the stomach) and would dispense the drug in a controlled fashion over a long period of time, i.e., in excess of twelve hours.
Such a device is illustrated by U.S. Pat. Nos. 3,901,232 and 3,944,064. This device comprises a collapsed support, on the outside of which is attached a means for dispensing drug and inside of which is a material that is solid or liquid at room temperature but becomes a gas at body temperature. When this device is swallowed, the material inside the support is converted into a gas and expands the support, thereby retaining the device within the stomach. While these devices are retained within the stomach for longer than the usual residence time, they suffer from several disadvantages. They require a number of assembling steps and thus are considerably more difficult to make than the conventional capsule or tablet. Moreover, the use of the easily vaporized material to inflate the collapsed support may have unwanted side effects when this vaporizable material is released from the device within the body.
Another example of such a device is that described in German Pat. No. 2,328,580 to Banker, which discloses and claims a device comprising a drug-containing core coated with a hydratable polymeric film. The film material swells due to hydration when in contact with gastric juice to a size sufficient to retain the device in the stomach.
However, prior art devices have various disadvantages, such as not being retained in the environment of use for a sufficient period of time, not providing a longer duration of drug action than conventional dosage forms, being difficult to manufacture, and the like.
The device of the present invention is designed to overcome these disadvantages of the prior art and to provide a means whereby prolonged internal administration of medicaments at a controlled rate is possible.